Gene therapy shows promise in eye disorders

LONDON - Toby Stroh was in his 20s when his doctor told him he would go blind in his 50s, and his years of playing tennis and being able to drive or work could be gone long before that.

LONDON — Toby Stroh was in his 20s when his doctor told him he would go blind in his 50s, and his years of playing tennis and being able to drive or work could be gone long before that.

Now, he’s 56, and two years have passed since his retina was deliberately infected with a virus carrying a gene to correct a protein deficiency that was destroying its cells. He’s still a regular on the tennis court and has a successful career in law.

“For the last 30 years, I’ve been living under the insidious inevitability of going blind,” Stroh said about his experimental treatment. “Now, there is a very real prospect I will continue to be able to see.”

Stroh is one of a handful of patients with an inherited cause of progressive blindness called choroideremia who took part in an early-stage trial of a gene-therapy treatment designed to correct a genetic defect that means retina cells gradually die.

Although the results are from only six patients in a Phase I trial, researchers said they suggest doing more studies to see whether similar gene therapies could be developed for other, more-common genetic causes of blindness, such as macular degeneration and retinitis pigmentosa.

Choroideremia is caused by a gene mutation and affects an estimated 1 in 50,000 people and causes sufferers — mostly men — to lose their sight gradually as the cells in the retina degenerate.

There is no licensed treatment for the condition, and the photoreceptor cells — the rods and cones in the retina that respond to light by sending signals to the brain — eventually die, leading to blindness by middle age.

In the trial, a team led by Robert MacLaren of the University of Oxford, a consultant surgeon at the Oxford Eye Hospital, injected the patients’ retinas with a genetically engineered virus to deliver a corrective copy of the gene to the appropriate part of the eye.

“The virus has to be delivered to the target cells, which are the cells of the retina,” MacLaren said.

To do that, the surgeon performs an operation similar to cataract surgery in which the patient’s retina is detached and lifted, and the virus is then injected with a fine needle.

“The virus goes in, infects the cells and puts the protein back into the cells — so we’re harnessing the capability of the virus to infect cells and deliver its DNA,” he said.

“This is the exciting thing about gene therapy,” said MacLaren, whose trial results were recently published in the journal Lancet. “We’re talking about a single one-off genetic correction … that has long-standing effects that so far have not been shown to diminish.”

The results showed that of the six patients treated — each of them only in one eye so that the other could act as a comparison — the two with the poorest sight before the gene therapy had significantly improved vision six months later.

In the other four patients, whose vision was only slightly impaired before treatment because they were at earlier stages of the condition, the results confirmed that the gene therapy is safe, with the virus delivering its DNA without damaging the retina.

“It is still too early to know if the … treatment will last indefinitely,” MacLaren said. “But we can say that the vision improvements have been maintained for as long as we have been following up with the patients, which is two years in one case.”

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